Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
Immunotherapies are beneficial for a considerable proportion of cancer patients, but ineffective in others. In vitro modelling of the complex interactions between cancer cells and their microenvironment could provide a path to understanding immune therapy sensitivity and resistance. Here we develop MIRO, a fully humanised in vitro platform to model the spatial organisation of the tumour/stroma interface and its interaction with immune cells. We find that stromal barriers are associated with immune exclusion and protect cancer cells from antibody-dependent cellular cytotoxicity, elicited by targeted therapy. We demonstrate that IL2-driven immunomodulation increases immune cell velocity and spreading to overcome stromal immunosuppression and restores anti-cancer response in refractory tumours. Collectively, our study underscores the translational value of MIRO as a powerful tool for exploring how the spatial organisation of the tumour microenvironment shapes the immune landscape and influences the responses to immunomodulating therapies.
Authors
- Maxime Cazorla (ORCID: https://orcid.org/0000-0002-8260-1154)
- Marta Garrido (ORCID: https://orcid.org/0000-0002-4049-7635)
- Jenniffer Linares (ORCID: https://orcid.org/0000-0001-9373-8781)
- Alba Recort-Bascuas
- Anna Labernadie (ORCID: https://orcid.org/0000-0001-5768-5088)
- Julien Colombelli (ORCID: https://orcid.org/0000-0002-2784-4276)
- Judith Linacero
- Teresa Galán
- Laura Comerma (ORCID: https://orcid.org/0000-0002-0249-4636)
- Alexandre Calon (ORCID: https://orcid.org/0000-0002-3398-6131)
- Anna Sallent-Aragay
- Xavier Trepat (ORCID: https://orcid.org/0000-0002-7621-5214)
- Joan Albanell (ORCID: https://orcid.org/0000-0003-1239-4580)
- Pere Roca‐Cusachs (ORCID: https://orcid.org/0000-0001-6947-961X)
- Ana Rovira (ORCID: https://orcid.org/0000-0003-1301-2599)
- Tom Golde (ORCID: https://orcid.org/0000-0002-3288-5646)
- Eleni Dalaka (ORCID: https://orcid.org/0000-0003-3306-7466)
- Patricia Fernández‐Nogueira (ORCID: https://orcid.org/0000-0002-7246-490X)
- Clément Hallopeau (ORCID: https://orcid.org/0000-0002-0692-2407)
- Elisa I. Rivas
- Alice Perucca (ORCID: https://orcid.org/0000-0003-1602-0199)
- Jordi Pastor Viel
- Xavier Badenas
- Andrea Gómez Llonín
- Oriol Mañé Benach
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Pompeu Fabra (ES)
- Instituto de Salud Carlos III (ES)
- Centre Tecnologic de Telecomunicacions de Catalunya (ES)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Institute for Research in Biomedicine (ES)
- Hospital Del Mar (ES)
- Barcelona Institute of Science and Technology (ES)
- Institute for Bioengineering of Catalonia (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Centro de Investigacion Principe Felipe (ES)
- University of Mauritius (MU)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-03
- DOI
- https://doi.org/10.1038/s41467-025-56275-1
- Citations
- 14
- Primary Topic
- Advanced Biosensing Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 11.28
Funders
- Fundació la Marató de TV3
- “la Caixa” Foundation
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad
- Institució Catalana de Recerca i Estudis Avançats
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red de Cáncer
- Xarxa de Bancs de Tumors de Catalunya
- Horizon 2020 Framework Programme
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación
- European Social Fund